The immune response elicited by mammary adenocarcinoma cells transduced with interferon-gamma and cytosine deaminase genes cures lung metastases by parental cells.
The parental cells of the TSA murine mammary adenocarcinoma (TSA-pc) were transfected with both the interferon-gamma (IFN-y) gene and the cytosine deaminase (CD) suicide gene to obtain a therapeutic vaccine active against TSA-pc lung metastases. Even in the absence of treatment with the prodrug 5-fluorocytosine (5-FC), the local growth of double transfectants (CD-y clones) was inhibited by a marked recruitment of granulocytes and macrophages. In mice harboring TSA-pc micrometastases, therapeutic vaccination with either IFN-gamma or CD single transfectants reduced the number of lung nodules, whereas CD-gamma double transfectants abrogated metastasis growth in up to 80% of mice. Treatment of mice with 5-FC did not alter the curative efficacy of CD-gamma double-transfectant cells. By contrast, in mice vaccinated with CD single-transfectant cells, 5-FC treatment caused a significant loss of their curative activity. Host T cells played an active role in the cure of lung metastases, because vaccination of nude mice with CD-gamma cells was uneffective.
Nanni
P
P
Institute for Cancer Research and Centro Interdipartimentale di Ricerche sul Cancro G. Prodi, University of Bologna, Italy.
De Giovanni
C
C
Nicoletti
G
G
Landuzzi
L
L
Rossi
I
I
Frabetti
F
F
Giovarelli
M
M
Forni
G
G
Cavallo
F
F
Di Carlo
E
E
Musiani
P
P
Lollini
P L
PL
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D043525:Cytosine Deaminase; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D007371:Interferon-gamma; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase